Comparable overall rates of TEAEs and SAEs vs Aubagio® (teriflunomide)1

Overall, the proportion of patients experiencing at least 1 treatment-emergent adverse event (TEAE) or serious adverse event (SAE) was similar across treatment groups.1

Adverse reactions (ARs) reported in at least 5% of patients taking PONVORY® and at a higher rate than in patients taking Aubagio®2

comparable rates of adverse reactions vs teriflunomide1

  • The most common ARs (incidence ≥10%) in patients taking PONVORY® were upper respiratory tract infection (37%), hepatic transaminase elevation (23%), and hypertension (10%)2
  • ARs reported in at least 2% to <5% of patients taking PONVORY® and at a higher rate than in patients taking Aubagio® included cough, pain in extremity, somnolence, pyrexia, increase in C-reactive protein, hypercholesterolemia, and vertigo2
  • 82% of patients taking PONVORY® completed 2 years of study treatment, compared with 82.2% of patients taking Aubagio®2

*Includes the following terms: nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, respiratory tract infection viral, viral upper respiratory tract infection, tracheitis, and laryngitis.2

Includes the following terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased.2

Includes the following terms: hypertension, hypertensive crisis, blood pressure increased, blood pressure systolic increased, blood pressure diastolic increased.2

Comparable overall rates of TEAEs and SAEs vs Aubagio®1

Comparable overall rates of TEAEs and SAEs vs Aubagio®1

Most frequent TEAEs (≥10%) in either group1

Most frequent treatment-emergent adverse events (TEAEs)

Increased ALT and nasopharyngitis were reported more frequently in patients taking PONVORY® than in patients taking Aubagio®.1

Headache and alopecia were more frequently reported in patients taking Aubagio®.1

Upper respiratory tract infection was reported by a similar percentage of PONVORY® and Aubagio® patients.1

Summary of liver test abnormalities1,2

  • The majority (89%) of patients with alanine aminotransferase (ALT) increases ≥3x the upper limit of normal (ULN) continued treatment with PONVORY® with values returning to <3x the ULN within approximately 2 to 4 weeks2
  • All ALT level increases of ≥3 the ULN resolved despite continued treatment with PONVORY® (n = 86) or after treatment discontinuation (n = 11).1
  • ALT increased ≥3x the ULN in 17.3% of patients taking PONVORY® compared with 8.3% of patients taking Aubagio®2
  • ALT increased ≥5x ULN in 4.6% of patients taking PONVORY® compared with 2.5% of patients taking Aubagio®2
  • ALT increased ≥8x ULN in 0.7% of patients taking PONVORY® compared with 2.1% of patients taking Aubagio®1
  • Patients who develop symptoms suggestive of hepatic dysfunction§ should have hepatic enzymes checked. PONVORY® should be discontinued if significant liver injury is confirmed2
Summary of liver test abnormalities1,2

ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBIL = total bilirubin; ULN = upper limit of normal.
Central laboratory reference ranges: ALT ULN: 44 U/L (male) and 33 U/L (female); AST ULN: 39 U/L (male) and 34 U/L (female).3

§Such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice, and/or dark urine during treatment.2

Patient with preexisting ALT elevation >5x ULN and resolved after discontinuation.3

Effects on heart rate and rhythm on Day 13#

Overview of treatment-emergent heart rate and rhythm (including hypotension) adverse events of special interest (AESI), safety set3

effects on heart rate and rhythm on Day 1

First dose monitoring is recommended for select patients2

Because initiation of PONVORY® treatment results in a decrease in heart rate (HR), first dose, 4-hour monitoring is recommended for patients with2:

  • Sinus bradycardia (HR <55 beats per minute [bpm])
  • First- or second-degree atrioventricular (AV) block (Mobitz type I)
  • History of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in stable condition

First dose monitoring should be completed in a setting where resources to appropriately manage symptomatic bradycardia are available.

In all patients, a dose titration is required for initiation of treatment with PONVORY® to help reduce cardiac effects2

In the OPTIMUM study:

  • Bradycardia at treatment initiation and sinus bradycardia on ECG|| occurred in 5.8% of patients taking PONVORY® compared with 1.6% of patients taking Aubagio®2
    • Bradycardia resolved in all patients without intervention and did not require discontinuation of treatment2
  • No second- and third-degree AV blocks were observed. AV conduction delays manifested as first-degree AV block (prolonged PR interval on ECG), which occurred in 3.4% of patients taking PONVORY® and in 1.2% of patients taking Aubagio®2
    • The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, resolved without intervention, and did not require discontinuation of treatment with PONVORY®2

AV = atrioventricular; ECG = electrocardiogram.

#These treatment-emergent AESI occurred following the PONVORY® 2 mg dose on Day 1, consistent with titration requirements for PONVORY®.2,3

||Defined as HR <50 bpm.2

50% of patients remained on PONVORY® 20 mg4

In the most recent analysis of an ongoing phase 2, long-term, safety extension study4:

50% of patients remained 
on PONVORY® 20 mg
after 8 years

The median exposure
to PONVORY® 20 mg
was 8 years

  • The data shown represent patients who initiated PONVORY® 20 mg treatment in the core study and continued with 20 mg during TP1 of the extension study4

TP = treatment period.

The study period consisted of a core study lasting 24 weeks and an extension study subdivided into 3 TPs. Additional patients received PONVORY® 10 mg (n = 139) or 40 mg (n = 15) (data not shown). Data were analyzed at the end of TP3 (March 2019). Patients with >8 years of PONVORY® 20 mg treatment exposure: n = 73; total patients receiving PONVORY® 20 mg: N = 145.4